阿黴素+Olaratumab對晚期軟組織肉瘤的生存期影響
作者：
小柯機器人發布時間：2020/4/14 12:52:53
美國斯隆·凱特琳紀念癌症中心William D. Tap聯合英國皇家馬斯登NHS基金會信託基金和癌症研究所Robin L. Jones團隊近日取得一項新成果。他們探討了阿黴素+Olaratumab與阿黴素+安慰劑對晚期軟組織肉瘤患者生存期的影響。該研究於2020年4月7日發表在《美國醫學會雜誌》上。
晚期軟組織肉瘤（STS）患者的平均總生存期不到2年。在一項臨床2期研究中，與僅使用阿黴素相比，向阿黴素中添加Olaratumab可增加患者的總體生存獲益。
為了確定阿黴素+Olaratumab對晚期/轉移性STS患者的療效，2015年9月至2018年12月，研究組在25個國家/地區的110個地點進行進行了一項確認性、臨床3期、雙盲、隨機試驗，招募了509名未接受過蒽環類藥物治療、不可切除的局部晚期或轉移性STS患者。將患者按1：1隨機分組，其中258例接受阿黴素+Olaratumab治療，251例接受阿黴素+安慰劑治療。
509例患者的平均年齡為56.9歲，女性佔58.2%，平滑肌肉瘤（LMS）患者佔46.0%，所有患者均納入初始分析。平均隨訪31個月後，阿黴素+Olaratumab組總STS的中位總生存期為20.4個月，阿黴素+安慰劑組為19.7個月；阿黴素+Olaratumab組LMS的中位總生存期為21.6個月，阿黴素+安慰劑組為21.9個月，差異均不顯著。總STS患者中超過15%的3級以上不良反應為中性粒細胞減少、白細胞減少或高熱性中性粒細胞減少。
總之，阿黴素+Olaratumab與阿黴素+安慰劑相比，對總體生存期並無明顯影響。
附：英文原文
Title: Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial
Author: William D. Tap, Andrew J. Wagner, Patrick Schffski, Javier Martin-Broto, Anders Krarup-Hansen, Kristen N. Ganjoo, Chueh-Chuan Yen, Albiruni R. Abdul Razak, Alexander Spira, Akira Kawai, Axel Le Cesne, Brian A. Van Tine, Yoichi Naito, Se Hoon Park, Alexander Fedenko, Zsuzsanna Pápai, Victoria Soldatenkova, Ashwin Shahir, Gary Mo, Jennifer Wright, Robin L. Jones
Issue&Volume: 2020/04/07
Abstract: Importance Patients with advanced soft tissue sarcoma (STS) have a median overall survival of less than 2 years. In a phase 2 study, an overall survival benefit in this population was observed with the addition of olaratumab to doxorubicin over doxorubicin alone.
Objective To determine the efficacy of doxorubicin plus olaratumab in patients with advanced/metastatic STS.
Design, Setting, and Participants ANNOUNCE was a confirmatory, phase 3, double-blind, randomized trial conducted at 110 sites in 25 countries from September 2015 to December 2018; the final date of follow-up was December 5, 2018. Eligible patients were anthracycline-naive adults with unresectable locally advanced or metastatic STS, an Eastern Cooperative Oncology Group performance status of 0 to 1, and cardiac ejection fraction of 50% or greater.
Interventions Patients were randomized 1:1 to receive doxorubicin, 75 mg/m2 (day 1), combined with olaratumab (n=258), 20 mg/kg in cycle 1 and 15 mg/kg in subsequent cycles, or placebo (n=251) on days 1 and 8 for up to 8 21-day cycles, followed by olaratumab/placebo monotherapy.
Main Outcomes and Measures Dual primary end points were overall survival with doxorubicin plus olaratumab vs doxorubicin plus placebo in total STS and leiomyosarcoma (LMS) populations.
Results Among the 509 patients randomized (mean age, 56.9 years; 58.2% women; 46.0% with LMS), all were included in the primary analysis and had a median length of follow-up of 31 months. No statistically significant difference in overall survival was observed between the doxorubicin plus olaratumab group vs the doxorubicin plus placebo group in either population (total STS: hazard ratio, 1.05 [95% CI, 0.84-1.30], P=.69, median overall survival, 20.4 months vs 19.7 months; LMS: hazard ratio, 0.95 [95% CI, 0.69-1.31], P=.76, median overall survival, 21.6 months vs 21.9 months). Adverse events of grade 3 or greater reported in 15% or more of total patients with STS were neutropenia (46.3% vs 49.0%), leukopenia (23.3% vs 23.7%), and febrile neutropenia (17.5% vs 16.5%).
Conclusions and Relevance In this phase 3 clinical trial of patients with advanced STS, treatment with doxorubicin plus olaratumab vs doxorubicin plus placebo resulted in no significant difference in overall survival. The findings did not confirm the overall survival benefit observed in the phase 2 trial.
DOI: 10.1001/jama.2020.1707
Source: https://jamanetwork.com/journals/jama/article-abstract/2764181